Sudomotor function for peripheral diabetic neuropathy evaluation

ABSTRACT

A method for assessing sudomotor function of a patient for evaluating diabetic and autonomous neuropathy is disclosed. The method is performed in a system comprising electrodes intended to be placed on different regions of the patient body, and an adjustable DC source. The method includes applying on the electrodes DC voltage pulses of varying voltage values in order to stress sweat glands, the voltage pulses lasting given durations allowing the stabilization of electrochemical phenomena in the body, near the electrodes; collecting data representative of the current between the electrodes, and of the potential generated on the electrodes for the different DC voltages; from the data, computing results representative of the electrochemical skin conductance of the patient; reconciling the latter data with reference data obtained in the same conditions on patients identified as suffering or not from sudomotor, and identifying the patient as suffering or not from sudomotor dysfunction.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/215,813, filed on Aug. 23, 2011, which is incorporated by referenceherein.

BACKGROUND OF THE INVENTION

1. Field

The invention relates in general to medical diagnostic devices andmethods in the field of human health. The invention more specificallyapplies to diagnostic of autonomic neuropathy, and in particular todiabetic polyneuropathy.

2. Description of the Related Art

Diabetic polyneuropathy (DPN) is partly a peripheral autonomicneuropathy (PAN) that is linked to lesions of small unmyelinated fibres.These unmyelinated fibers, including those that innervate the sweatglands, are the first to undergo damage. As such, DPN is anerve-length-dependent process that firstly affects the feet.

Peripheral autonomic neuropathy (PAN) results in the atrophy of sweatglands and decreased sudomotor response that may affect the skinsuppleness and flexibility that prevent skin cracks and ulceration, andmay also reduce sweating, leading to abnormal skin conditions such asdryness, fissures and blisters.

Moreover, PAN results in decreased foot sensitivity. The prevalence ofPAN has recently been estimated to affect 43% of diabetic patients aged40-70 years. Early detection of symmetrical distal sensory-motor DPN candecrease morbidity and the risk of foot complications.

Sensory function is considered one of the major initiating risk factorsin the pathogenesis of diabetic foot ulcer. As no gold standard isavailable for early diagnosis of DPN, vibration perception threshold(VPT), using a biothesiometer, and pressure perception, usingSemmes-Weinstein monofilaments, have been proposed to identify patientsat risk, but none of these investigates peripheral autonomicinvolvement.

Peripheral autonomic neuropathies such as DPN are also usually evaluatedthrough sudomotor function, using the sympathetic skin response (SSR),or by quantitative sudomotor axon reflex testing (QSART). These methodsrequire specialized training to perform and are also time-consumingprocedures. Neuropad® is another alternative test targeted for use bythe patient, although it is less sensitive and semi-quantitative.

Thus, the need for highly trained personnel, lack of sensitivity,non-quantitative results and time required to take measurements haverestricted the widespread use of sudomotor function assessment inclinical practice. There is therefore a need for an alternative methodfor detecting peripheral autonomic neuropathies such as diabeticpolyneuropathy through assessment of sudomotor function.

SUMMARY OF THE INVENTION

Thus, the object of the present invention is to provide a new method forquickly assessing sudomotor function of a patient throughelectrochemical skin conductance (ESC) evaluation. Another objet of theinvention is to provide a non-invasive and quantitative measurement thatis easy to implement on a patient.

According to the invention, a method for diagnosing a patient, byassessment of sudomotor function based on ESC evaluation through reverseiontophoresis is provided. In a preferred embodiment, the method isperformed in a system comprising an anode and a cathode, intended to beplaced on different regions of the patient body, and an adjustable DCsource, which is controlled in order to feed the anode with a DCcurrent, and comprises the step consisting of:

-   -   applying DC voltage pulses of varying voltage values in order to        stress sweat glands, the voltage pulses lasting given durations        allowing the stabilization of electrochemical phenomena in the        body in the vicinity of the electrodes,    -   collecting data representative of the current between the anode        and the cathode, and of the potential generated on the cathode        through reverse iontophoresis for the different DC voltages,    -   from said data, computing results representative of the        electrochemical skin conductance of the patient,    -   reconciling said data representative of the electrochemical skin        conductance of the patient with reference data obtained in the        same conditions on patients identified as suffering or not from        autonomic neuropathy, and identifying the patient as suffering        or not from sudomotor dysfunction.

The computation step may comprise the computation of electrochemicalskin conductance values at given voltages, by computing the ratiobetween the current generated through the anode and the cathode, and theresulting voltage drop between anode and cathode. In some embodiments,the patient is identified as suffering from diabetes, and thereconciliation step allows identifying the patient as suffering or notfrom diabetes polyneuropathy.

The method may further comprise at least one test among the following:peripheral vibration sensation through evaluation of the vibrationperception threshold, cardiac autonomic neuropathy (CAN) assessment,neuropathy assessment through Michigan neuropathy screening instrument(MNSI).

BRIEF DESCRIPTION OF THE DRAWINGS

The features and advantages of the invention will be apparent from thefollowing more detailed description of certain embodiments of theinvention and as illustrated in the accompanying drawings, in which:

FIG. 1 shows a system for designed to carry out the method according tothe invention.

FIG. 2 shows the main steps carried out in the diagnosis methodaccording to the invention.

FIG. 3 is a schematic representation of an eccrine gland that transportthe DC current in the electrolyte (sweat), with chloride at anode andproton at cathode.

FIG. 4 shows the results of statistical analyses carried out with themethod according to the invention.

FIG. 5 a shows comparison of clinical, biochemical characteristics andconductance measurement in patients with clinical neuropathy accordingto MNSI B score.

FIG. 5 b shows comparison of clinical, biochemical characteristics andconductance measurement in patients with increasing vibration perceptionthreshold.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT Description of aDiagnosis System According to the Invention

A system 100 for assessing the sudomotor function of a patient throughreverse iontophoresis is shown on FIG. 1. The system 100 comprises aseries of large area electrodes 110, preferably four electrodes 110, onwhich the patient can place his hands and feet. The sites of theelectrodes 110 have been chosen because of their high density of eccrinesweat glands.

The electrodes 110 can be made of nickel or stainless steel withsufficient level of nickel. Their individual surface area is comprisedbetween 50 cm² and 200 cm², so that they cover substantially all thesurface of the hand palms and of the feet soles. Yet they can be adaptedfor children or even infants.

They are connected to a computer 120 for collecting, computing, andstoring data. They are also connected to an adjustable DC source 130,which is controlled by an operator or the computer 120 to feed theelectrodes 110 with a DC current of a determined voltage. The system 100also comprises a measuring circuit 130, to measure the voltage potentialof each electrode through a voltmeter 131, as well as the currentbetween two electrodes through a Wheatstone bridge 132. The diagnosingsystem can also be equipped with a display 121, designed for displayingthe measured data as well as the results of the computations carried outon said data.

The diagnosis method 200 according to the invention will now bedescribed in reference to FIG. 2.

Measurement Step 201

In order to assess sudomotor function of a patient, in view of detectingautonomic neuropathy, the patient places his/her hands and/or feet onthe large area nickel electrodes 110, and stands up without moving hishands and/or feet during the 2 minutes that lasts the measurement. Atthe low DC voltages applied to the skin, typically less than 10 V, theoutermost layer of the skin, called Stratum Corneum (SC), iselectrically insulating and only the appendageal pathway is conductive,so that only the eccrine sweat glands are stressed. The fact that theseglands are the most numerous and present at almost all parts of theskin, and in abundance (500 per cm2) at hand palm and foot sole, allowsan effective electrical response of the skin.

For the measurement 201, the electrodes are used alternatively as ananode and as a cathode and a DC incremental voltage <10 V is applied atanode. Up to twenty pulses are applied, each of duration between 0.5 sand 1 s, which allows the stabilisation of electrochemical phenomenatowards steady states in the body, in the vicinity of the electrodes.The pulse voltages are increased and/or decreased between for example 1V and 4 V approximately.

The electrochemical phenomena are measured by two active electrodes (theanode and the cathode) successively and independently for the two feetand for the two hands. The two other passive electrodes allow retrievalof the potential reached by the body. The applied voltage on the anodeinduces, through reverse iontophoresis, a voltage on the cathode andgenerates a current (intensity of around 0.2 mA). It is carried acrossthe gland by chloride and proton, is going through the body betweenanode and cathode and is directly related to ESC.

FIG. 3 is a schematic view of an eccrine gland stressed by an electrodeE. An eccrine gland comprises the secretory part SP, where the sweat isfiltered from blood plasma in a coil, and the excretory part EP, wheresome species can move in both sides (entry or absorption according totheir electrochemical gradient) across some ionic channels in a ductalmost straight that leads to a pore P on the skin surface. The StratumCorneum SC is represented on the skin surface.

ESC is neither influenced by the Stratum Corneum thickness, nor thesweat conductivity. It is the lateral surface conductance of the wall ofthe gland which is measured. As chloride is produced by sweat glands,when the latter is stressed by the electric field created by theelectrodes, the current generated between the electrodes isrepresentative of the sudomotor function which is impaired by peripheralautonomic neuropathies such as diabetic polyneuropathy.

The measurement of the current through the electrodes and voltages ofactive and passive electrodes thus allows assessing the sudomotorfunction of the sweat glands. Both electrodes voltages and currentbetween them are measured and stored by the computer 120 at measurementstep 201. The same series of measurements can then be carried out withthe electrodes being reversed (anode becoming cathode and vice-versa),and the same can be carried out on the feet/hands.

Computation 202

Once the electrodes potentials have been recorded, the computer 120determines the electrical skin conductance (ESC) of the patient bycalculating the ratio between the current generated through the activeelectrodes and the resulting voltage drop between anode and cathode. Theelectrical skin conductance can be plotted for each voltage valueapplied to the anode. In that case, the plot can be displayed on thedisplay 121.

Comparison with Healthy Patients 203

ESC values are then compared to traditional tests results for assessingautonomic neuropathies, in order to check the indications given by theESC results. A large-scale experiment was carried out on 265 consecutivediabetic patients, by implementing on them the method according to theinvention, as well as traditional tests such as Ewing's cardiacautonomic function tests and Heart Rate Variability analysis (HRV),vibration perception threshold measurement (VPT), and neuropathyassessment using the Michigan Neuropathy Screening Instrument (MNSI).

Patients were accepted on the condition of having had a diagnosis oftype 2 diabetes. Exclusion criteria were patients taking drugs thatwould have an effect on the sympathetic system such as beta blocker,amputation of arms or legs, electrical implantable device(pacemaker/defibrillator), sensitivity to nickel or any other standardelectrodes, suffering from seizures, epilepsy or proliferativeretinopathy, suffered Myocardial infarction (MI) and/or stroke in thepast 6 months, arrhythmia's, treatment with anti-arrhythmic drugs andany advanced systemic condition.

Ewing's cardiac autonomic function tests comprise four tests. Each testwas carried out according to the standard procedure described by Ewinget al in:

“Diagnosis and management of diabetic autonomic neuropathy” (Ewing D J,Clarke B F, Br Med J 1982; 285:916-918)

-   -   HRV during deep breathing test (E/I ratio): R-R intervals during        inhalation and exhalation are calculated. The longest R-R        interval is determined during expiration (R-R max) and the        shortest interval during inspiration (R-R min). The result is        then expressed as the ratio of the heart rate at expiration to        that at inspiration and is called as E/I ratio. Normal values        are superior to 1.21.    -   HRV during standing test (30/15 ratio): shortest R-R interval is        measured after standing when heart rate is maximum, which is        around the 15^(th) beat. This is followed by bradycardia which        is indicated by the longest R-R interval around 30^(th) beat.        The ratio of longest to shortest R-R is calculated which is also        called as 30/15 ratio. Normal values are superior to 1.03.    -   HRV during Valsalva maneuver test: the heart rate rises during        the maneuver and after the maneuver the heart rate slows. In        this test the ratio of longest r-R interval after maneuver to        shortest R-R interval during the maneuver is calculated. Normal        values are superior to 1.20.    -   Blood pressure response to standing (Orthostatic Blood Pressure        Response): the postural fall in the blood pressure is taken as        the difference between the systolic blood pressure lying and        standing. Normal fall is inferior to 20 mmHg.

An abnormality in at least two tests is required to ensure the diagnosisof Cardiac Autonomic Neuropathy (CAN). Vibration Perception Threshold(VPT) was measured on both sides using a biothesiometer on the plantarside of the great toe on a continuous scale. The mean between the twosides was used for analysis. Four groups were then defined: VPT<10 V: noneuropathy, VPT between 10 and 15 V: mild neuropathy, VPT between 15 and25 V: moderate neuropathy, and VPT superior to 25 V: severe neuropathy.

The neuropathy assessment through use of Michigan neuropathy ScreeningInstrument (MNSI) was implemented with both a questionnaire to recordneuropathic symptoms (MNSI A), and clinical assessment, including footinspection (deformities, skin changes and infection), ankle reflextesting, vibration sensation using 128 Hz tuning fork and touchsensation perception using 10-g Semmes-Weinstein monofilament (MNSI B).Biochemical analyses were also performed.

Non-fasting blood sample was collected in EDTA vacutainer, and processedto obtain plasma. Plasma aliquots were stored (−70° C.) until furtheranalysis. Hemoglobin was measured on whole blood on a Beckman CoulterAnalyzer (AC.T diff™, Miami, Fla., USA). Plasma glucose, uric acid,creatinine, Gamma-GT, SGPT and SGOT and urine creatinine were measuredon an automated biochemistry analyzer (Hitachi 902, Germany), usingstandard enzymatic methods. HbA1c was measured using HPLC method onBioRad-D10 (US) Plasma B12 and folate were measured by microbiologicalassays. Urine albumin was measured using an immunoprecipitation assayand albumin-creatinine ratio was calculated.

The results of this experiment, which are discussed hereinafter, areshown on FIG. 4, FIG. 5 a and FIG. 5 b. FIG. 4 shows clinicalcharacteristics of the patients and their biothesiometer reading and CANresults by categories of decreasing feet ESC distribution. P-values arecalculated using Simple Linear Regression Analysis for continuousvariables and Chi square proportion trend test for categoricalvariables.

FIG. 5 a shows clinical, biochemical characteristics and hands and feetESC values in patients with and without clinical neuropathy. P-valueswere calculated using Kruscal-Wallis test for continuous variables.

FIG. 5 b shows Clinical, biochemical characteristics and hands and feetESC values in patients with increasing degrees of VPT. P-values werecalculated using Kruskal-wallis test for continuous variables andchi-square trend test for categorical variables.

Data are presented as median (25th-75th percentile). Normality of thevariables was checked and appropriate transformations were done.Following variables needed transformation: Log transformation for FolicAcid, Biothesiometer, Maximum/Minimum 30/15 Ratio and Valsalva maneuver,log-log transformation for B12 and E/I Ratio, and square roottransformation for Michigan Score A. Agreement between left and rightelectrode readings for different sites was investigated using meanpercent difference and Coefficient of Variation (CV). Simple linearregression analysis was used to study the association of hands and feetESC with continuous measurements such as biothesiometer, MNSI and CAN.Agreement between biothesiometer readings, MNSI score and feet ESCvalues was studied using simple linear regression analysis withprediction interval by calculating percentage of observation outside theprediction limit.

Low percentage indicates good agreement. Independent biologicaldeterminants were tested using multiple linear regression analysis. Areaunder the curve (AUC) of the ROC curve was calculated to measure theefficiency of feet ESC in diagnosing patients with and withoutneuropathy based on VPT value.

As visible on FIG. 4, lower ESC reading was significantly associatedwith higher age, longer duration of DM, higher HbA1c, lower hemoglobinand higher plasma vitamin B12 concentration. There was no differencebetween men and women. BMI, WHR, non-fasting plasma glucose, plasmafolate, creatinine and uric acid concentrations and eGFR were notrelated to feet ESC.

Multiple linear regression analysis was performed to investigateindependent biological determinants of ESC. Lower ESC was associatedwith higher age and higher HbA1c (p<0.05, both) but not with gender,anthropometric and other biochemical parameters. Lower ESC wassignificantly associated both with increasing symptoms (MNSI A),(p<0.05) and increasing score on physical abnormalities suggestive ofperipheral neuropathy (MNSI B), (p<0.01). Lower ESC was alsosignificantly associated with increasing VPT measured by biothesiometer(p<0.01), and with higher number of abnormal CAN results (p<0.05).

Of the four CAN tests, lower feet ESC was associated with increasingpostural fall in blood pressure (corresponding to sympatheticabnormality) (p<0.05), but not with other CAN tests. Patients withESC<40 μS were more than 4 times likely to have 2 or more CAN testabnormal compared to patients with ESC>40 μS (OR 4.41 (1.72-11.29).

Correlation between VPT, MNSI and feet ESC was tested by simple linearregression analysis with prediction interval. VPT and MNSI wereregressed on ESC and the predicted VPT and MNSI measurements werecalculated for any observed value of ESC. Percentage of observationsoutside prediction interval was 2.6% for MNSI A, 1.5% for MNSI B and4.5% for VPT, which indicates good correlation. Similar results wereobtained for hands ESC.

The ability of feet ESC measurement to detect neuropathy againstbiothesiometer (VPT>20V) as measured by AUC was 0.70 (ROC curve). At 40μS sensitivity was 0.50 and specificity was 0.78 and at 60 μSsensitivity was 0.75 and specificity 0.54.

Diagnosis Step 204

The method according to the invention allows assessing sudomotorfunction through evaluation of electrochemical skin conductance (ESC).In particular, feet electrochemical skin conductance appears verydiscriminative for sudomotor dysfunction diagnosis. A poor feet ESC canhelp identify patients with early small unmyelinated nerve-fibredysfunction, and thus early autonomic neuropathy.

The results also show that the assessment of sudomotor dysfunction basedon ESC through reverse iontophoresis is a quantitative reproduciblemethod linked to cardiac autonomic neuropathies tests like Ewing testsand Heart Rate Variability analysis which is not influenced byglycaemia. In addition Foot ESC correlates with different degrees ofperipheral sensory neuropathy, as estimated by VPT measurement andmonofilament tests, and there is also progressive worsening of ESCmeasurements with increasing sensory perception threshold as estimatedby VPT or monofilament results.

The association of sensory loss and sudomotor dysfunction as evaluatedaccording to the present invention is also indicative of foot ulcerrisk. Finally, evaluation of ESC is a simple and quick method, whichdoes not require highly trained personnel.

The invention claimed is:
 1. A sudomotor diagnostic device comprising:(a) foot-contacting electrodes each having a surface area of at leastfifty cm²; (b) hand-contacting electrodes each having a surface area ofat least fifty cm²; (c) direct current operably sent to at least one ofthe electrodes; and (d) a computer connected to the electrodes, thecomputer operably determining electrical skin conductance by calculatinga relationship between current generated through the electrodes whichare active and a resulting voltage drop between the electrodes which areanodes and cathodes, and the computer making the determination withintwo minutes from the direct current initially being sent.
 2. The deviceof claim 1, wherein voltage applied on the anode electrodes induces,through reverse iontophoresis, a voltage on the cathode electrodes whichgenerates the current sent to the computer, and the direct currentapplied to a patient's hands and feet by the electrodes in less than tenvolts.
 3. The device of claim 1, wherein the computer compares thedetermined conductance to reference data, the computer diagnoses if asudomotor dysfunction exists and displays results on acomputer-controlled display.
 4. The device of claim 1, furthercomprising an adjustable direct current source sending the directcurrent to the electrodes.
 5. The device of claim 1, wherein each of theelectrodes includes nickel material which contacts substantially all ofa palm surface of the associated hand or sole surface of the associatedfoot.
 6. The device of claim 1, wherein each of the electrodes includesstainless steel which contacts substantially all of a palm surface ofthe associated hand or sole surface of the associated foot.
 7. Thedevice of claim 1, wherein the computer determines if a patient hasdiabetes.
 8. The device of claim 1, wherein the computer determines if apatient has diabetes polyneuropathy.
 9. The device of claim 1, whereinthe computer uses data based on peripheral vibration sensation of apatient through evaluation of a vibration perception threshold.
 10. Thedevice of claim 1, wherein the computer uses data based on cardiacautonomic neuropathy assession.
 11. The device of claim 1, wherein thecomputer uses data based on a neuropathy assessment through a Michiganneuropathy screening instrument.
 12. A sudomotor diagnostic devicecomprising: (a) electrodes having a surface area of at least fifty cm²;(b) an adjustable direct current source adapted to feed at least some ofthe electrodes with direct current to operably cause reverseiontophoresis; (c) the electrodes being alternately used as an anode anda cathode with current pulses, each of one second or less, being appliedat the anode of less than ten volts; and (d) a computer adapted todiagnose sudomotor dysfunction and output its results on a displaywithin two minutes from initial reverse iontophoresis.
 13. The device ofclaim 12, wherein the electrodes include patient hand-contactingelectrodes and patient foot-contacting electrodes.
 14. The device ofclaim 13, wherein each of the electrodes includes nickel material whichcontacts substantially all of a palm surface of the associated hand orsole surface of the associated foot.
 15. The device of claim 13, whereineach of the electrodes includes stainless steel which contactssubstantially all of a palm surface of the associated hand or solesurface of the associated foot.
 16. The device of claim 12, wherein thecomputer compares measured patient electrochemical data to previouslystored healthy patient data.
 17. The device of claim 12, wherein thecomputer determines if a patient has diabetes.
 18. A sudomotordiagnostic device comprising: (a) electrodes each being adapted tocontact against substantially all of a sole surface of a patient's foot;(b) additional electrodes each being adapted to contact againstsubstantially all of a palm surface of a patient's hand; and (c) acomputer connected to the hand and foot electrodes and being adapted todetermine patient sudomotor dysfunction, if present, when direct currentof less than ten volts is operably sent to at least one of theelectrodes to cause eccrine sweat glands of the patient to produce anelectrochemical change measured by the computer.
 19. The device of claim18, wherein the computer measures and stores electrode voltage andcurrent data, and the computer causes the electrodes to be electricallyreversed such that an anode of the electrodes becomes a cathode of theelectrodes and vice-versa.
 20. The device of claim 18, wherein thecomputer determines electrical skin conductance of the patient fromcurrent generated through active of the electrodes and a resultingvoltage drop between an anode and a cathode of the electrodes, with thecomputer outputting the determination using a display.
 21. The device ofclaim 18, wherein voltage applied on an anode of the electrodes induces,through reverse iontophoresis, a voltage on a cathode of the electrodeswhich generates current sent to the computer.
 22. The device of claim18, further comprising an adjustable direct current source sending thedirect current to at least some of the electrodes, and the computercomparing measured data associated with the patient electrochemicalchange to previously stored healthy patient data
 23. The device of claim18, wherein the computer determines if the patient has diabetes.
 24. Thedevice of claim 18, wherein the computer determines the sudomotordysfunction within two minutes of when the direct current is initiallysent to the electrodes.
 25. The device of claim 18, wherein the computerassesses severity of the sudomotor dysfunction.
 26. The device of claim18, wherein the computer uses data from at least one test among thefollowing: peripheral vibration sensation through evaluation of avibration perception threshold, cardiac autonomic neuropathy (CAN)assessment, or neuropathy assessment through a Michigan neuropathyscreening instrument (MNSI).
 27. The device of claim 18, wherein thecomputer reconciles computed electrochemical skin conductance valueswith at least one other measurement, as a co-indicator of sudomotordysfunction and diabetic polyneuropathy severity.
 28. The device ofclaim 18, wherein the computer determines severe sudomotor dysfunctionby low electrochemical skin conductance values in correlation with ahigh sensory perception threshold.
 29. The device of claim 18, whereinthe computer determines severe peripheral neuropathy by lowelectrochemical skin conductance values in correlation with high numberof abnormal CAN results.
 30. The device of claim 18, wherein thecomputer determines severe peripheral neuropathy by low electrochemicalskin conductance values in correlation with data assessed by MNSI.
 31. Asudomotor diagnostic device comprising: (a) foot-contacting electrodes;(b) hand-contacting electrodes; (c) a direct current power sourceconnected to the electrodes; (d) a computer connected to the electrodes;(e) voltage applied on an anode of the electrodes inducing, throughreverse iontophoresis, a voltage on a cathode of the electrodes whichgenerates a signal sent to the computer which it uses to determineelectrochemical skin conductance values; and (f) the computeradditionally receiving data associated with at least one of: (i)peripheral vibration sensation through evaluation of a vibrationperception threshold, (ii) cardiac autonomic neuropathy assessment(CAN), or (iii) neuropathy assessment through a Michigan neuropathyscreening instrument (MNSI), as a co-indicator of at least one of:sudomotor dysfunction or diabetic polyneuropathy severity.
 32. Thedevice of claim 31, wherein the computer compares measured patientelectrochemical data to previously stored healthy patient data.
 33. Thedevice of claim 31, wherein the computer compares the determined patientconductance with reference data, the computer diagnoses if a patientsudomotor dysfunction exists and displays results on acomputer-controlled display.
 34. The device of claim 31, wherein each ofthe electrodes includes nickel material which contacts substantially allof a palm surface of an associated hand or sole surface of an associatedfoot.
 35. The device of claim 31, wherein each of the electrodesincludes stainless steel which contacts substantially all of a palmsurface of an associated hand or sole surface of an associated foot. 36.The device of claim 31, wherein the computer measures and storeselectrode voltage and current data, and the computer causes theelectrodes to be electrically reversed such that an anode becomes acathode and vice-versa.
 37. The device of claim 31, wherein the computerdetermines electrical skin conductance from current generated throughactive of the electrodes and a resulting voltage drop between an anodeand a cathode of the electrodes, with the computer outputting thedetermination using a display.
 38. The device of claim 31, wherein thecomputer determines the sudomotor dysfunction within two minutes whendirect current is initially sent to the electrodes.